The objective of this project is to establish the primary site of diabetic microangiopathy of the retina in order to contribute to the prevention of devastating vascular pathology. This will be accomplished by the following methods: (a) Comparative ultrastructural and biochemical studies of pathognomonic vascular lesions in human diabetes and experimentally induced animal diabetes. We attribute leakage of the retinal vascular wall, an early sign of retinopathy, to the disruption of the blood-barrier between the basement membrane and the Muller-cell network. Alloxan- and streptozotocin-induced diabetic conditions were basically alike; streptozotocin was used in the studies because it acts more selectively on beta cells. (b) Establishment of an animal model of diabetic hypertensive diseases. Diabetes was induced in spontaneously hypertensive rats (a model of essential hypertension) and in Wistar rats treated with a silver clip on the renal artery to induce Goldblatt-type renal hypertension. Streptozotocin hindered development of hypertension in SHR rats. Application of the renal clip to streptozotocin-diabetic Wistar rats hindered development of hypertension by hindering growth--attempts are being made to find the cause of this problem. (c) Studies of renal vascular lesions in mice with encephalo-myocarditis-virus-induced diabetes (a model of juvenile-onset diabetes).